Ammonia → Trichlorourethan

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Reaction Steps

Me-PRX (150 g) is dissolved in toluene (450 ml) at room temperature. The mixture is then heated to reflux. At reflux, 2,2,2-trichloroethyl-chloroformate (120 ml) is added dropwise for about 2.5 hours. After about 3 hours at reflux, the reaction mixture is cooled, and ammonia 20% (300 ml) and water (300 ml) is added. The organic phase is separated and washed with water (500 ml), followed by brine (500 ml). The organic phase is then separated, dried over MgSO4, filtered. Toluene is then removed under reduced pressure to give 280.2 g of the 2,2,2-trichloroethyl carbamate of paroxetine. The carbamate is then hydrolyzed according to procedures set forth, for example, in Examples 5-7 to give paroxetine base. Paroxetine base may then be converted into the desired polymorphic form of, e.g., the hydrochloride acid addition salt such as the hemihydrate, anhydrate or solvate form as disclosed herein.

Provenance & Evidence